Curcumin synthase

Curcumin synthase categorizes three enzyme isoforms (CURS1, 2, and 3), type III polyketide synthases (PKSs) present in the leaves and rhizome of the turmeric plant (Curcuma longa) that synthesize curcumin. CURS1-3 are responsible for the hydrolysis of feruloyldiketide-CoA, previously produced in the curcuminoid pathway, and a decarboxylative condensation reaction that together comprise one of the final steps in the synthesis pathway for curcumin, demethoxycurcumin, and bisdemethoxycurcumin, the compounds that give turmeric both its distinctive yellow color, and traditional medical benefits. CURS should not be confused with Curcuminoid Synthase (CUS), which catalyzes the one-pot synthesis of bisdemethoxycurcumin in Oryza sativa.

Structure

Crystallization studies have determined that curcumin synthase is a homodimer of ketosynthase subunits. Each includes a highly conserved Cys (164), His (303), Asn (336) catalytic triad, and CURS1 has been shown to exhibit the αβαβα folding pattern, conserved features of type III PKSs.

The catalytic triads are independent of each other and are contained in the center of each monomer, connected to the surface with a CoA binding tunnel. While CURS1, 2, and 3 share approximately 80% amino acid sequence identity, their small structural differences account for their differences in preferred starter substrates and most prolific product.

The well conserved catalytic triad sits at the end of a hydrophobic cavity, referred to as the CoA binding tunnel, that allows for the specificity of curcumin synthase for the CoA moiety. The triad, displayed in a PyMOL image below, despite being buried in each monomer, is connected to the surface of the binding tunnel, allowing interactions with substrates. The pockets of the protein show this tunnel and where the β-keto acid tail of feruloyl-CoA can fit into, which we can also see in the photo of the CoA binding tunnel reaching towards the catalytic triad.